Sydney Rice

Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders

OBJECTIVEnThe aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID).nnnMETHODSnFourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and optimal dose for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD).nnnRESULTSnMPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects.nnnCONCLUSIONnThe predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.

Brain imaging as a predictor of early functional outcome following traumatic brain injury in children, adolescents, and young adults.

Objectives:A depth of lesion (DOL) model using brain imaging has been proposed to aid in medical decision-making and planning for rehabilitation resource needs. The purpose of this study was to determine the early prognostic value of a DOL classification system for children and young adults following severe traumatic brain injury. Methods and Outcome measures:CT/MRI brain imaging studies on 92 patients, aged 3 to 21, admitted to the Kluge Childrens Rehabilitation Center, University of Virginia, were evaluated to determine DOL. Images were classified according to 5 DOL levels (cortical to brainstem). Functional outcomes in mobility, self-care, and cognition, as rated on the WeeFIM instrument, were compared by DOL levels. Results:Admission WeeFIM scores were significantly different for the DOL levels with the highest score for frontal and/or temporal lesions and the lowest for lesions including the brainstem or cerebellum (P < .001). However, the deeper the lesion, the greater the functional gains (P = .05), resulting in discharge WeeFIM scores that were not significantly different across DOL levels. Patients with deeper lesions tended to have longer lengths of stay in rehabilitation but were able to “catch up” with patients who had more superficial lesions. Conclusions:While relatively simple and convenient, the DOL classification system is limited in its usefulness as an early prognostic tool. It may not be possible to predict outcome in the early acute phase in the intensive care unit on the basis of standard brain imaging alone. Patients with deeper lesions may enter rehabilitation at a more impaired level but can make remarkable progress, though it may take longer than for less severely injured individuals.

Assessment of Cognitive Scales to Examine Memory, Executive Function and Language in Individuals with Down Syndrome: Implications of a 6-month Observational Study

Down syndrome (DS) is the most commonly identifiable genetic form of intellectual disability. Individuals with DS have considerable deficits in intellectual functioning (i.e., low intellectual quotient, delayed learning and/or impaired language development) and adaptive behavior. Previous pharmacological studies in this population have been limited by a lack of appropriate endpoints that accurately measured change in cognitive and functional abilities. Therefore, the current longitudinal observational study assessed the suitability and reliability of existing cognitive scales to determine which tools would be the most effective in future interventional clinical studies. Subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Clinical Evaluation of Language Fundamentals-Preschool-2 (CELF-P-2), and the Observer Memory Questionnaire-Parent Form (OMQ-PF), Behavior Rating Inventory of Executive Function®–Preschool Version (BRIEF-P) and Leiter International Performance Scale-Revised were assessed. The results reported here have contributed to the optimization of trial design and endpoint selection for the Phase 2 study of a new selective negative allosteric modulator of the GABAA receptor α5-subtype (Basmisanil), and can be applied to other studies in the DS population.

Prospective, Naturalistic, Pilot Study of Open-Label Atomoxetine Treatment in Preschool Children with Attention-Deficit/Hyperactivity Disorder

OBJECTIVEnThe aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD).nnnMETHODSnNine boys and 3 girls (mean age = 5.0 +/- 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day.nnnRESULTSnThere was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 +/- 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions-Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Childrens Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 +/- 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to chest ache. There were no changes in weight, height, or cardiovascular measures.nnnCONCLUSIONnThis open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this.

Incidence of delirium in children with cancer.

There are limited data on the incidence of delirium in children with cancer. We performed a retrospective chart review of all pediatric oncology admissions over a 1 year period to determine the incidence of delirium in this population. We identified seven patients with delirium (10% incidence). Delirium is associated with significant morbidity and mortality, and is likely under‐recognized in this population. Improved diagnosis and treatment of delirium may improve outcomes in children with cancer. Pediatr Blood Cancer 2014;61:2094–2095.

Effect of shortened length of stay on functional and educational outcome after pediatric rehabilitation.

Rice SA, Allaire J, Elgin K, Farrell W, Conaway M, Blackman JA: Effect of shortened length of stay on functional and educational outcome after pediatric rehabilitation. Am J Phys Med Rehabil 2004;83:27–32. ObjectiveThe purpose of this study was to assess changes in the length of stay and its effect on effectiveness and return to school in an inpatient pediatric rehabilitation unit during a 5-yr period from fiscal year 1997 through 2001. DesignWe reviewed prospectively collected data for a cohort of 321 children during fiscal years 1997–2001. ResultsLength of stay was significantly shortened, with mean lengths of stay of 58.9, 43.5, 30.7, 40.9, and 24.0 days in years 1997 through 2001, respectively. Change in length of stay remained significantly decreased after adjusting for age, sex, admission diagnosis, admission severity, and type of health insurance. There was no difference in mean change in effectiveness measured by change in admission and discharge WeeFIM® ratings. There were significant differences across years in the educational placement of children at discharge, with a declining trend in the proportion of children discharged to classroom-based educational services. ConclusionThere was a reduction in inpatient length of stay during a 5-yr period for children in this pediatric rehabilitation setting. During this time, there was no change in the effectiveness of rehabilitation as measured by functional outcome. However, using return to a classroom setting as a marker of reintegration into routine activities, fewer children returned to a similar level of community participation.

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome

Abstract We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing (WGS) and mRNA sequencing (RNA-seq) were performed on a family having an affected proband, his unaffected parents, and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild-type TATA-box-binding protein factor 1 (TAF1), deletion of TAF1, and TAF1 variant p.Ser1600Gly samples. The whole genome data identified several gene variants. However, the genome sequence data failed to implicate a candidate gene as many of the variants were of unknown significance. By combining genome sequence data with transcriptomic data, a probable candidate variant, p.Ser1600Gly, emerged in TAF1. Moreover, the RNA-seq data revealed a 90:10 extremely skewed X-chromosome inactivation (XCI) in the mother. Our results showed that neuronal ion channel genes were differentially expressed between TAF1 deletion and TAF1 variant p.Ser1600Gly cells, when compared with their respective controls, and that the TAF1 variant may impair neuronal differentiation and cell proliferation. Taken together, our data suggest that this novel variant in TAF1 plays a key role in the development of a recently described X-linked syndrome, TAF1 intellectual disability syndrome, and further extends our knowledge of a potential link between TAF1 deficiency and defects in neuronal cell function.

Postfolate spina bifida lesion level change

Spina bifida accounts for a large proportion of birth defects in the United States. Studies have evaluated the decrease in prevalence at birth after folate fortification of food grains, but little is known about neurologic functional changes related to fortification. This study assesses the functional level of lesions in the prefortification and postfortification eras.

Understanding the Natural Progression of Spina Bifida: Prospective Study

Background Spina bifida (SB) is monitored through birth defects surveillance across the United States and in most developed countries. Although much is known about the management of SB and its many comorbid conditions in affected individuals, there are few systematic, longitudinal studies on population-based cohorts of children or adults. The natural history of SB across the life course of persons with this condition is not well documented. Earlier identification of comorbidities and secondary conditions could allow for earlier intervention that might enhance the developmental trajectory for children with SB. Objective The purpose of this project was to assess the development, health, and condition progression by prospectively studying children who were born with SB in Arizona and Utah. In addition, the methodology used to collect the data would be evaluated and revised as appropriate. Methods Parents of children with SB aged 3-6 years were eligible to participate in the study, in English or Spanish. The actual recruitment process was closely documented. Data on medical history were collected from medical records; family functioning, child behaviors, self-care, mobility and functioning, and health and well-being from parent reports; and neuropsychological data from testing of the child. Results In total, 152 individuals with SB were identified as eligible and their parents were contacted by site personnel for enrollment in the study. Of those, 45 (29.6%) declined to participate and 6 (3.9%) consented but did not follow through. Among 101 parents willing to participate, 81 (80.2%) completed the full protocol and 20 (19.8%) completed the partial protocol. Utah enrolled 72.3% (73/101) of participants, predominately non-Hispanic (60/73, 82%) and male (47/73, 64%). Arizona enrolled 56% (28/50) of participants they had permission to contact, predominately Hispanic (18/28, 64%) and male (16/28, 57%). Conclusions We observed variance by site for recruitment, due to differences in identification and ascertainment of eligible cases and the required institutional review board processes. Restriction in recruitment and the proportion of minorities likely impacted participation rates in Arizona more than Utah.